Xanthoceraside inhibits pro-inflammatory cytokine expression in Aβ25-35/IFN-γ-stimulated microglia through the TLR2 receptor, MyD88, nuclear factor-κB, and mitogen-activated protein kinase signaling pathways.

An accumulating body of evidence suggests that Alzheimer's disease (AD) is associated with microglia-mediated neuroinflammation and pro-inflammatory cytokine expression. Therefore, the suppression of neuroinflammation and pro-inflammatory cytokine might theoretically slow down the progression of AD. Xanthoceraside, a novel triterpenoid saponin extracted from the husks of Xanthoceras sorbifolia Bunge, has potent antiinflammatory and neuroprotective effects. However, the molecular mechanism underlying its anti-inflammatory action remains unclear. In the present study, we attempted to determine the effects of xanthoceraside on the production of pro-inflammatory mediators in amyloid β25-35 (Aβ25-35)/interferon-γ (IFN-γ)-stimulated microglia. Our results indicated that xanthoceraside (0.01 and 0.1 μM) significantly inhibited the release of nitric oxide (NO) and pro-inflammatory cytokines interleukin-1β and tumor necrosis factor-α in a concentration-dependent manner. Reverse transcriptase-polymerase chain reaction and western blotting analyses showed that xanthoceraside decreased the Aβ25-35/IFN-γ-induced production of cyclooxygenase-2 and inducible NO synthase. These effects were accompanied by inhibited activities of nuclear factor-κB and mitogen-activated protein kinase through Toll-like receptor 2 in a myeloid differentiation protein 88-dependent manner. Our results provide support for the therapeutic potential of xanthoceraside in AD.